Role of Animal Models in Coronary Stenting

Abstract

Coronary angioplasty initially employed balloon dilatation only. This technique revolutionized the treatment of coronary artery disease, although outcomes were compromised by acute vessel closure, late constrictive remodeling, and restenosis due to neointimal proliferation. These processes were studied in animal models, which contributed to understanding the biology of endovascular arterial injury. Coronary stents overcome acute recoil, with improvements in the design and metallurgy since then, leading to the development of drug-eluting stents and bioresorbable scaffolds. These devices now undergo computer modeling and benchtop and animal testing before evaluation in clinical trials. Animal models, including rabbit, sheep, dog and pig are available, all with individual benefits and limitations. In smaller mammals, such as mouse and rabbit, the target for stenting is generally the aorta; whereas in larger animals, such as the pig, it is generally the coronary artery. The pig coronary stenting model is a gold-standard for evaluating safety; but insights into biomechanical properties, the biology of stenting, and efficacy in controlling neointimal proliferation can also be gained. Intra-coronary imaging modalities such as intravascular ultrasound and optical coherence tomography allow precise serial evaluation in vivo, and recent developments in genetically modified animal models of atherosclerosis provide realistic test beds for future stents and scaffolds.

A Comparison of Fully-Coupled 3D In-Stent Restenosis Simulations to In-vivo Data

“…Experimental studies associate extensive damage to the artery and related high injury score with increased neointima thickness and larger incidence of clinically recognised restenosis (Gunn et al, 2002; Morton et al, 2004; Iqbal et al, 2016). Injury is caused by stent malapposition, artery curvature, and high balloon-to-artery ratio.…”

“…For this study a vessel with IS 2 was selected, since this is a typical injury score in in-vivo studies (Gunn et al, 2002; Morton et al, 2004; Iqbal et al, 2016). The time course of reendothelization severely affects both the maximal neointimal thickness and the time when this thickness is reached.…”

Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity

“…The researchers concluded that the cardiac lesions developed in rabbit hearts after single dose x-ray exposure resembled the lesions seen in humans [40]. Rabbits have since only been used by a few researchers to study RIHD [41,[114][115][116][117][118], although this species is commonly used to study cardiovascular disease from other causes [119][120][121][122][123][124][125]. There might be unique benefits to studying electrophysiological changes caused by radiation in rabbit models over rat models, as the rabbits' Ca2+ transport, action potential duration, and main ionic currents underlying repolarization are similar to humans [113,126,127].…”

Uncertainty Quantification of a Multiscale Model for In-Stent Restenosis

“…8, invivo animal experiments, reviewed e.g., in Ref. 9, and also by using computational models. 3,5,13,18,34 The computational models of ISR usually represent cells by agents, either freely moving 5,18,34 or placed on a lattice.…”